rs9061

chr2-230212395-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):c.619G>A(p.Glu207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,608 control chromosomes in the GnomAD database, including 9,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (742 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8945 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.444

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052110553).
• BP6: Variant 2-230212395-C-T is Benign according to our data. Variant chr2-230212395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 334910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.619G>A	p.Glu207Lys	missense_variant	5/19	ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.619G>A	p.Glu207Lys	missense_variant	5/19	2	NM_080424.4	P1

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14243 AN: 152122 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.0975

GnomAD3 exomes AF: 0.111 AC: 27759 AN: 251134 Hom.: 2021 AF XY: 0.118 AC XY: 16068 AN XY: 135698

Gnomad AFR exome AF: 0.0756

Gnomad AMR exome AF: 0.0432

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.0580

Gnomad NFE exome AF: 0.0966

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.101 AC: 147593 AN: 1460368 Hom.: 8945 Cov.: 31 AF XY: 0.106 AC XY: 77078 AN XY: 726556

Gnomad4 AFR exome AF: 0.0808

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.0597

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0936 AC: 14257 AN: 152240 Hom.: 742 Cov.: 32 AF XY: 0.0945 AC XY: 7038 AN XY: 74442

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.0596

Gnomad4 NFE AF: 0.0966

Gnomad4 OTH AF: 0.0970

Alfa AF: 0.101 Hom.: 448

Bravo AF: 0.0899

TwinsUK AF: 0.0930 AC: 345

ALSPAC AF: 0.0851 AC: 328

ESP6500AA AF: 0.0776 AC: 342

ESP6500EA AF: 0.0938 AC: 807

ExAC AF: 0.114 AC: 13871

Asia WGS AF: 0.168 AC: 584 AN: 3478

EpiCase AF: 0.0975

EpiControl AF: 0.0985

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	5.2
Dann	Benign	0.60
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.70	T;T;T;T;T;T
MetaRNN	Benign	0.0052	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N;N;.;N;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N;N;N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.20	T;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T;.
Polyphen		0.049	B;B;B;.;.;.
Vest4		0.16
MPC		0.34
ClinPred		0.010	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9061; hg19: chr2-231077110; COSMIC: COSV51246462; COSMIC: COSV51246462;